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With the emergence of COVID-19, there is an increased focus in human literature on cytokine production, the implications of cytokine overproduction, and the development of novel cytokine-targeting therapies for use during sepsis. In addition to viral infections such as COVID-19, bacterial infections resulting in exposure to endotoxins and exotoxins in humans can also lead to sepsis, resulting in organ failure and death. Like humans, horses are exquisitely sensitive to endotoxin and are among the veterinary species that develop clinical sepsis similar to humans. These similarities suggest that horses may serve as a naturally occurring model of human sepsis. Indeed, evidence shows that both species experience cytokine dysregulation, severe neutropenia, the formation of neutrophil extracellular traps, and decreased perfusion parameters during sepsis. Sepsis treatments that target cytokines in both species include hemoperfusion therapy, steroids, antioxidants, and immunomodulation therapy. This review will present the shared cytokine physiology across humans and horses as well as historical and updated perspectives on cytokine-targeting therapy. Finally, this review will discuss the potential benefits of increased knowledge of equine cytokine mechanisms and their potential positive impact on human medicine.

An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Cell-free DNA (cfDNA) is fragmented extracellular DNA that is released from cells into various body fluids. Previously published data from adult horses supports cfDNA as a potential disease biomarker, but also shows that direct measurement in plasma is inaccurate due to matrix effect. It is currently unknown whether a similar matrix effect exists in foal plasma. Given this, the objectives of the current study were to investigate foal plasma for potential matrix effect during fluorescence measurement of cfDNA using a Qubit fluorometer, and to determine whether neat and/or extracted plasma cfDNA concentrations are significantly different in healthy, sick non-septic (SNS) or septic foals. We hypothesized that matrix effect would interfere with accurate fluorescent measurement of cfDNA in foal plasma. Further, we hypothesized that mean extracted cfDNA concentrations, and/or extracted cfDNA:neutrophil ratio, would be elevated in plasma of septic foals compared to healthy or SNS foals. Cell-free DNA was measured in neat plasma, and following DNA extraction with a commercial kit, from 60 foals. Foal plasma exhibited both autofluorescence and non-specific dye binding, confirming matrix effect. However, even with extraction, no significant difference was found in cfDNA concentrations, or cfDNA:neutrophil ratios, between healthy (sepsis score ≤ 5), SNS (sepsis score 6-11 and negative blood culture), or septic (sepsis score ≥ 12 ± positive blood culture) foals. Our data show that matrix effect interferes with accurate Qubit measurement of cfDNA in foal plasma and supports previous findings that plasma cfDNA concentrations are not associated with sepsis diagnosis in foals. Further research is needed to better understand neutrophil function and dysfunction in foal sepsis.

The number of companion pigs in the US is increasing, as is the frequency with which they present to primary companion care practices. However, pigs are often an understudied species in veterinary curricula, and many students graduate from veterinary school with minimal porcine handling experience. Coupled with the poor peripheral vascular access associated with pigs, this presents a challenge for many new graduates and other primary care veterinarians seeking to improve their knowledge of porcine handling, anatomy, and medical care. Furthermore, much of the available veterinary literature regarding porcine venous access is dated, limited to technical notes, or inaccessible to many primary care veterinarians. This review aims to supplement this lack of knowledge by discussing techniques in restraint, sedation, venipuncture, and catheterization of companion pigs as a reference for veterinarians and researchers alike.

Objective: Develop, implement, and monitor for adverse effects of, a novel hemoperfusion therapy in adult horses., Methods: A prospective, observational feasibility study using three healthy adult horses from the North Carolina State University teaching herd. Health status was determined by physical exam, complete blood count, coagulation panel, and serum biochemistry. Each horse was instrumented with a 14 Fr × 25 cm double-lumen temporary hemodialysis catheter and underwent a 240 min polymer-based hemoperfusion session. Horses were administered unfractionated heparin to maintain anti-coagulation during the session. Given the novelty of this therapy in horses, each horse was treated as a learning opportunity that informed an iterative process of protocol development and modification., Measurements and Main Results: Our long-term goal is to investigate potential clinical applications of hemoperfusion in horses, including cytokine reduction in horses with severe SIRS/sepsis. Horses were monitored for changes in clinical exam, biochemistry and hematology parameters. Additionally, cytokines were quantified to determine whether extracorporeal hemadsorption therapy alone caused an inflammatory response. Our results show that hemoperfusion therapy was associated with decreased platelet counts and serum albumin concentration. There was no significant change in plasma cytokine concentrations with hemoperfusion therapy. In one horse, the cytokine concentrations decreased, as previously reported with hemoperfusion therapy in humans., Hypothesis: We hypothesized that hemoperfusion therapy could be performed in healthy adult horses without significant adverse effects., Conclusion: Polymer-based hemoperfusion is a feasible extracorporeal therapy (ECT) modality for adult horses. Additional studies are needed to further establish clinical protocols, as well as establish efficacy of polymer-based hemoperfusion for treatment of various conditions in horses, including intoxications, immune-mediated conditions, and sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hobbs, Le Sueur, Burke, Cooper, Sheats and Ueda.)

Objective: Plasma cytokine adsorption has shown benefit as an adjunctive therapy in human sepsis but has yet to be investigated in horses. We hypothesized that ex vivo filtration of equine plasma with a novel cytokine adsorption device would significantly reduce concentrations of lipopolysaccharide-stimulated cytokines. We also hypothesized that the device would adsorb medications commonly used to treat sepsis., Animals: 8 horses owned by North Carolina State University., Methods: Four liters of heparinized whole blood was collected from healthy adult horses (n = 8) and stimulated with lipopolysaccharide (100 ng/mL) for 6 hours (37 °C.) from June 4, 2023, to December 15, 2023. Plasma was filtered through a cytokine adsorption device or sham circuit. Samples were collected at 11 time points for multiplex cytokine analysis. Chemistry analysis was performed before and after filtration. To investigate the impact of the device on medication concentrations, equine plasma containing potassium penicillin, gentamicin, and flunixin meglumine was filtered through the cytokine adsorption device or sham for 6 hours. Drug concentrations before and after filtration were determined by ultra-high-performance liquid chromatography. Prefiltration versus postfiltration sample concentrations were analyzed by Student paired t test using GraphPad Prism 9.0 (P < .05)., Results: Filtration of lipopolysaccharide-stimulated equine plasma (n = 8) for 6 hours resulted in significant mean reductions in the cytokines IL-10, IL-5, IL-8, tumor necrosis factor-α (TNF-α), and IL-1β, as well as albumin. Drug concentrations of potassium penicillin, gentamicin, and flunixin meglumine were also significantly reduced by filtration., Clinical Relevance: This work provides proof of concept for further investigation of extracorporeal cytokine adsorption as a potential adjunct treatment for equine sepsis.

Background: Over-the-wire (OTW) catheter placement is performed frequently in horses. Intravascular loss of a guidewire has been anecdotally reported, but there is limited information regarding the treatment and outcome of horses that have experienced this complication of OTW catheter placement., Objectives: Describe the clinical and diagnostic features, treatment, and outcome of horses experiencing IV guidewire loss at the time of OTW catheter placement., Animals: Thirteen horses., Methods: Multicenter retrospective study to identify horses with IV guidewire loss. Horses of all ages were considered for inclusion. Horses were excluded from the study if complete medical records of signalment, indication, and outcome were not available. Intravenous guidewire loss was defined as the guidewire being lost IV at the time of OTW catheter placement., Results: No horses in this study experienced adverse clinical signs associated with the loss of a guidewire. Eight horses had the guidewire removed and the guidewire was left in situ in 5 horses. None of the horses with the guidewire in situ had experienced long-term effects., Conclusions and Clinical Importance: Intravenous guidewire loss seems to have a good long-term prognosis even in horses in which removal of the guidewire was not possible. Thus, in horses where guidewire removal is not feasible, guidewires that remain in situ may have limited to no adverse effects., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Limited information is available regarding endothelial glycocalyx degradation during sepsis in horses. Plasma syndecan-1 concentrations are increased in consequence of sepsis in other species and have been useful for prognostication., Objectives: To determine whether plasma syndecan-1 levels are increased in adult horses affected with sepsis., Study Design: Retrospective cohort study., Methods: Adult horses were assigned to one of three groups based on results of physical and laboratory examinations, clinical diagnosis, and results of previously described SIRS classification: Group 1 horses included healthy, nonseptic horses; Group 2 included horses in which clinical illness was identified but that were not considered to be septic; Group 3 included horses with a clinical diagnosis of sepsis. Plasma syndecan-1 concentration was determined in blood obtained at admission into the hospital for each horse, using an equine specific ELISA. Data were analysed using ANOVA and linear regression (p ≤ 0.05)., Results: One hundred and ninety-one horses were included and divided into three groups. Scores for SIRS were highest for Group 3 horses and lowest in Groups 1 and 2. Plasma syndecan-1 concentrations in Group 3 horses (50.73 ± 84.24 μg/ml; n = 42) were greater than those for Group 1 (15.69 ± 11.28 μg/ml; n = 66) and Group 2 (16.88 ± 15.30 μg/ml; n = 83). There was no difference regarding syndecan concentrations between Groups 1 and 2., Main Limitations: Retrospective study design, solitary time point of measurement for each patient, and lack of a widely accepted consensus regarding definitive diagnosis of sepsis in adult horses., Conclusions: Circulating plasma levels of syndecan-1, a biochemical marker of endothelial glycocalyx damage, are increased in septic adult horses., (© 2022 EVJ Ltd.)

Biomarkers are typically proteins, enzymes, or other molecular changes that are elevated or decreased in body fluids during the course of inflammation or disease. Biomarkers pose an extremely attractive tool for establishing diagnoses and prognoses of equine gastrointestinal colic, one of the most prevalent causes of morbidity and mortality in horses. This topic has received increasing attention because early diagnosis of some forms of severe colic, such as intestinal ischemia, would create opportunities for rapid interventions that would likely improve case outcomes. This review explores biomarkers currently used in equine medicine for colic, including acute phase proteins, proinflammatory cytokines, markers of endotoxemia, and tissue injury metabolites. To date, no single biomarker has been identified that is perfectly sensitive and specific for intestinal ischemia; however, L-lactate has been proven to be a very functional and highly utilized diagnostic tool. However, further exploration of other biomarkers discussed in this review may provide the key to accelerated identification, intervention, and better outcomes for horses suffering from severe colic.

Objective: To determine whether anesthesia type (sedation or general anesthesia) affects kid survival to discharge in caprine cesarean sections (C-sections)., Animals: Retrospective cohort of 99 caprine C-sections (2011-2021)., Procedures: All surgeries were performed via left flank laparotomy in right lateral recumbency. The number of kids alive at presentation, surgery, and discharge was recorded. Kids that were dead on presentation or euthanized intraoperatively were excluded. Goats were classified as "healthy" (American Society of Anesthesiologists status ≤ 2) or "sick" (≥ 3)., Results: Kid survival was significantly higher for C-sections performed under sedation (47/52 [90%]) than for C-sections performed under general anesthesia (16/24 [66%]; P = .004). Relative risk was 1.4 and odds ratio was 4.7., Clinical Relevance: Performing C-sections in sedated goats may improve kid survival rates over those under general anesthesia.

Magnetic resonance imaging is increasingly available for evaluation of horses with suspected pituitary adenomas; however, published studies describing the MRI features of normal equine pituitary glands are currently lacking. This retrospective, descriptive, anatomic study describes the MRI appearance and size of presumed normal equine pituitary glands and assesses potential correlations between pituitary size, brain size, and patient weight. These findings serve as a reference for MRI evaluation of the equine pituitary gland. Inclusion criteria consisted of adult horses (2-15 years old), over 300 kg with no evidence of Pituitary pars intermedia dysfunction (PPID) and no pituitary abnormalities identified with MRI, yielding 27 horses. Histology was available on seven pituitary glands; all were considered normal by a board-certified anatomic pathologist. Imaging features of the glands were evaluated on T2-weighted and pre- and postcontrast T1-weighted images. Pituitary length, width, and height and brain height and width were measured by two authors on transverse and mid-sagittal plane postcontrast T1 weighted images. The mean ± SD pituitary gland width was 21.0 ± 2.4 mm, height: 10.4 ± 1.9 mm, and length: 24.5 ± 2.7 mm. There were no significant correlations using a Pearson's correlation coefficient between pituitary and brain measurements, pituitary measurement, and body weight, or between brain measurements and body weight. A statistical difference was not identified using an unpaired t-test (p > 0.05) in pituitary and brain measurements between necropsied and non-necropsied horses. Relative to the cerebral white matter, all pituitary glands were isointense to slightly hyperintense on T1-weighted images and isointense on T2-weighted images, with the exception of a focal T1-weighted hyperintensity that was present in the caudal aspect of the pituitary gland in 88% of horses. All pituitary glands were homogenously contrast enhancing. Pituitary dimensions did not correlate with either brain size or body weight in horses., (© 2022 American College of Veterinary Radiology.)

Background: Pigs have an indiscriminate eating behavior placing them at high risk of developing foreign body (FB) obstructions., Objectives: Describe the clinical and diagnostic features, treatments, and outcome of pet pigs diagnosed with gastrointestinal (GI) FBs. Medical and surgical treatments, pig outcomes, and post-mortem findings were also investigated., Animals: Seventeen pet pigs., Methods: A multicenter retrospective study was conducted. Gastrointestinal FBs were defined as swallowed objects that became lodged within the gastrointestinal tract distal to the cardia identified during exploratory laparotomy., Results: Common clinical signs were anorexia/hyporexia, tachypnea, vomiting, dehydration, tachycardia, and ileus. Diagnostic imaging identified the presence of a FB in 4 cases. Upon celiotomy, the FBs were in the stomach and small intestine in 17 cases and large colon in 2 cases. Types of FB included fruit pit, diaper, and metallic objects. Of the 17 pigs, 15 (88%) were discharged from the hospital and 2 (12%) were euthanized., Conclusion and Clinical Importance: Clinical signs of GI FB were similar to those reported in obstipated pigs. Diagnostic imaging has limitations for detection of FB. Surgical removal of FBs in pigs carried a good prognosis., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Clinical features and patient outcomes for pet pigs with obstipation are poorly defined. This retrospective study reports the clinical findings from 24 pet (non-production) pigs with obstipation presented to 2 veterinary teaching hospitals. Clinical features of obstipated pet pigs included anorexia or hyporexia in 24 pigs (100%), pain on abdominal palpation in 22 (90%), lethargy in 21 (88%), tachypnea in 19 (79%), vomiting in 14 (58%), and tachycardia in 13 (54%). Frequently observed hematologic and biochemical abnormalities included leukopenia in 36% (8/22) of the pigs, lymphopenia in 75% (17/22), toxic changes in neutrophils in 63% (14/22), hypokalemia in 50% (9/18), and hypoglycemia in 28% (5/18). Diagnostic imaging via radiography and/or computed tomography frequently identified gastric distention and accumulation of ingesta and gas throughout the gastrointestinal tract. Medical treatments included fluid therapy, anti-emetics, oral administration of carbonated beverages, non-steroidal anti-inflammatory drugs, and systemic antimicrobials. Surgical intervention was performed in 7/29% of pigs. In this study, obstipation in pet pigs carried a fair to favorable prognosis for survival, with 70% of patients surviving to discharge., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)